An unprecedented expansion of knowledge has occurred in modern immunology in the field of innate immunity over the last 15 years. The Signaling Pathways in Innate Immunity (SPII) Training Program represents a revised, new T32 application to support 2 predoctoral and 2 postdoctoral trainees in this important and burgeoning area. The University of Maryland, School of Medicine (UMSOM) has significant research and training strengths in this area. The Training Grant Faculty (TGF) for this unique and highly focused program are drawn primarily from the Department of Microbiology and Immunology and several interdisciplinary centers and institutes at UMSOM including the Mucosal Biology Research Center, the Center for Vascular and Inflammatory Diseases, the Center for Vaccine Development, Greenebaum Cancer Center, and the Institute of Human Virology. All but one TGF are located within a 2-block distance of the Department of Microbiology & Immunology on the UMSOM campus. The TGF have a longstanding history of collaboration on grants and publications, and are well funded, with grants and contracts totaling ~$17.4 million in annual direct costs. Predoctoral trainees will be drawn primarily from the interdepartmental Graduate Program in Life Sciences (GPILS) Programs in Molecular Microbiology & Immunology (MMI) and Molecular Medicine (MM), established Ph.D. Programs that include a common core curriculum, program-specific courses, elective courses, journal clubs, seminars, annual symposia, and graduate research presentation days. Additional academic work will be combined with rigorous laboratory training through laboratory rotations and dissertation research under the direction of the TGF whose documented expertise will provide inter- and multidisciplinary training opportunities. Predoctoral students are selected from an increasingly qualified applicant pool, as well as from the UMSOM M.D./Ph.D. Program. Similarly, our Training Grant Eligible postdoctoral trainees are increasingly gravitating to laboratories with expertise in innate immune signaling. Both pre- and postdoctoral trainees will have additional didactic and non-didactic requirements, including training in the responsible conduct of research and professional development, as well as a highly structured mentoring program. Specific efforts are already in place to recruit trainees from underrepresented minorities. The program is guided by a highly qualified team including the Training Program Director, two Co-Directors, a Steering Committee, and an External Advisory Committee comprised of internationally recognized experts in innate immunity. We anticipate that our trainees will be extraordinarily well prepared for future careers in academia, government, and industry and will contribute in significant ways to basic and translational problems in this complex area of innate immunity.